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In fit patients, one year of venetoclax plus obinutuzumab (with or without ibrutinib) clearly beat the old chemotherapy standard.
Co-primary endpoints: uMRD at month 15 (GIV 92.2%, GV 86.5%, RV 57.0%, CIT 52.0%) and PFS (GIV and GV superior to CIT; RV not). 5-year PFS: GIV 81.3%, GV 69.8%, RV 57.4%, CIT 50.7%; 5-year OS 91-95% in all arms. NEJM 2023; 5-year update 2025-26. Showed that venetoclax needs obinutuzumab rather than rituximab, and that adding ibrutinib improves PFS at the cost of more toxicity.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
926 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Undetectable MRD at month 15 (blood)primary | GIV | - | 92.2% | - | - | link |
| GV | - | 86.5% | ||||
| RV | - | 57% | ||||
| Chemoimmunotherapy | - | 52% | ||||
| Progression-free survival at 5 years | GIV | - | 81.3% | - | - | link |
| GV | - | 69.8% | ||||
| RV | - | 57.4% | ||||
| Chemoimmunotherapy | - | 50.7% |
AMPLIFY delivered the first all-oral, fixed-duration doublet for front-line CLL and supported its approval, giving fit patients a way to avoid both chemotherapy and years of continuous BTK inhibitor. It does not settle whether a doublet or triplet is best, or how AV compares with venetoclax-obinutuzumab. Patients with TP53 aberration were excluded and still need different strategies.
CLL14 established the first chemotherapy-free, fixed-duration regimen for front-line CLL and made MRD-guided thinking mainstream in the disease. Patients get a year of treatment and then a treatment-free period rather than indefinite therapy. The choice today is between fixed-duration venetoclax combinations and continuous BTK inhibitors, with no proven survival difference.
Shares German CLL Study Group, Venetoclax + obinutuzumab (12 months), Michael Hallek, CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients.
Shares IGHV mutational status, AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, Obinutuzumab, BTK (Bruton tyrosine kinase).
Shares AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients, Obinutuzumab, BTK (Bruton tyrosine kinase), Chronic lymphocytic leukaemia, first treatment.
Shares BCL-2 inhibitors, Obinutuzumab, BTK (Bruton tyrosine kinase), Chronic lymphocytic leukaemia, first treatment.
Shares MRD-negative complete remission, BTK (Bruton tyrosine kinase), Chronic lymphocytic leukaemia, first treatment, Ibrutinib.
Shares BCL-2 inhibitors, Obinutuzumab, Chronic lymphocytic leukaemia, first treatment, Venetoclax.
Shares IGHV mutational status, Obinutuzumab, Chronic lymphocytic leukaemia, first treatment, Ibrutinib.
Shares BCL-2 inhibitors, Obinutuzumab, Chronic lymphocytic leukaemia, first treatment, Venetoclax.